Screening for an AIRE-1 mutation in patients with Addison's disease, type 1 diabetes, Graves' disease and Hashimoto's thyroiditis as well as in APECED syndrome

OBJECTIVE Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (A PECED) is a rare systemic autoimmune disorder of monogenic and autosomal-re cessive inheritance. To date, 29 APECED causing mutations have been identif ied in the responsible gene AIRE-1, coding for a regulator of transcription . The aim of this study was to examine whether mutations in AIRE-1, in thei r heterozygous form, predispose to the more common isolated autoimmune endo crinopathies Addison's disease, type 1 diabetes mellitus, Graves' disease a nd Hashimoto's thyroiditis. DESIGN Patients with isolated autoimmune endocrine disorders as well as hea lthy controls were analysed for two of the most common AIRE-1 mutations, mu tation R257X in exon 6 and a 13-bp deletion in exon 8. Mutations were detec ted by polymerase chain reaction based techniques. PATIENTS In total, 726 individuals were investigated for mutation R257X. Su bjects comprised patients with Addison's disease, IDDM, Graves' disease and Hashimoto's thyroiditis. With regard to the 13 bp deletion we could screen 91 patients with Addison's disease. In addition, six patients with the APE CED syndrome including one family were analysed for both mutations. RESULTS Out of the 12 alleles in APECED patients six contained either mutat ion R257X or the 13 bp deletion, confirming that these mutations prevail in Europe. R257X was found in one subject with Hashimoto's thyroiditis in its heterozygous form. The 13 bp deletion was not detected in any subject with Addison's disease. CONCLUSIONS The two studied AIRE-1 mutations are so rare in the general pop ulation that they can not contribute to susceptibility for the more common isolated autoimmune disorders.